Effect of oral CCK-1 agonist GI181771X on fasting and postprandial gastric functions in healthy volunteers
| Autor: | E. J. Castillo, Robin L. O'Connor-Semmes, Ann Louise Walker, Debra Stephens, Silvia Delgado-Aros, Anne Shachoy-Clark, Alan R. Zinsmeister, Duane Burton, Michael Camilleri |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Adult
Male Agonist medicine.medical_specialty Physiology medicine.drug_class Neuropeptide GASTRIC FUNCTIONS Gastroenterology Benzodiazepines Double-Blind Method Reference Values Physiology (medical) Internal medicine medicine Humans Cholecystokinin Dose-Response Relationship Drug Hepatology Gastric emptying business.industry Stomach digestive oral and skin physiology Fasting Postprandial Period Solutions medicine.anatomical_structure Endocrinology Postprandial Gastric Emptying Chemokines CC Female Chemokines Gallbladder Emptying business Tablets |
| Zdroj: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 287:G363-G369 |
| ISSN: | 1522-1547 0193-1857 |
| DOI: | 10.1152/ajpgi.00074.2004 |
| Popis: | CCK influences satiation and gastric and gallbladder emptying. GI181771X is a novel oral CCK-1 agonist; its effects on gastric emptying of solids, accommodation, and postprandial symptoms are unclear. Effects of four dose levels of the oral CCK-1 agonist GI181771X and placebo on gastric functions and postprandial symptoms were compared in 61 healthy men and women in a randomized, gender-stratified, double-blind, double-dummy placebo-controlled, parallel group study. Effects of 0.1, 0.5, and 1.5 mg of oral solution and a 5.0-mg tablet of GI181771X on gastric emptying of solids by scintigraphy, gastric volume by 99mTc-single photon emission computed tomographic imaging, maximum tolerated volume of Ensure, and postprandial nausea, bloating, fullness, and pain were studied. On each of 3 study days, participants received their randomly assigned treatment. Adverse effects and safety were monitored. There were overall group effects of GI181771X on gastric emptying ( P < 0.01) and fasting and postprandial volumes ( P = 0.036 and 0.015, respectively). The 1.5-mg oral solution of GI181771X significantly delayed gastric emptying of solids ( P < 0.01) and increased fasting ( P = 0.035) gastric volumes without altering postprandial ( P = 0.056) gastric volumes or postprandial symptoms relative to placebo. The effect of the 5.0-mg tablet on gastric emptying of solids did not reach significance ( P = 0.052). Pharmacokinetic profiles showed the highest area under the curve over 4 h for the 1.5-mg solution and a similar area under the curve for the 0.5-mg solution and 5-mg tablet. Adverse effects were predominantly gastrointestinal and occurred in a minority of participants. GI181771X delays gastric emptying of solids and exhibits an acceptable safety profile in healthy participants. CCK-1 receptors can be modulated to increase fasting gastric volume. |
| Databáze: | OpenAIRE |
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